The long-term objective of this project is development of effective methods for control of relative and absolute stereochemistry in the synthesis of conformationally-flexible, biologically-important molecules. During the first five years of the study attention was concentrated on a study of the stereochemistry of the addition of preformed lithium enolates to aldehydes (aldol additon reaction). A number of useful reagents were developed and applications in the total synthesis of macrolide antibiotics were initiated. In the coming grant period, it is intended to complete a total synthesis of erythronolide A and carry out syntheses of methynolide and tylonolide. In addition, research on the application of stereoselective aldol technology to the total synthesis of rare carbohydrates will continue. It is also planned to use methodology developed earlier in the project for elucidation of the stereochemistry of the biosynthetically-important archaebacterial lipids. The possible utility of the kinetic Michael addition of amide enolates to enones will be evaluated as a method for realizing stereocontrol. Four important carbon-carbon bond-forming reactions involving organosilicon compounds will be systematically investigated from a stereochemical standpoint. Finally, the use of chiral auxillaries for achieving absolute asymmetric induction in the addition of metal enolates to aldehydes and ketones will be studied.